The emergence of Omicron has prompted widespread speculation that it may be more resistant to Covid-19 vaccines than existing variants, including Delta. But what does that mean for the average double-vaccinated person?
All the vaccines currently available in the UK work by training the immune system against the coronavirus spike protein – the key it uses to infect cells by binding to the ACE2 receptor. Omicron possesses more than 30 mutations in this protein, including 10 in the so-called “receptor-binding domain” (RBD) – the specific part that latches on to this receptor. Delta has two RBD mutations.
However, even with all these changes, there will still be areas (epitopes) to which antibodies and T cells – which grow in response to previous infection or vaccination – will be able to respond.
“If you scribble the mutations on to a picture of the spike protein’s crystal structure, and relate that to all of the main antibody activities that we know about, it looks kind of terrifying – like, most of your key, neutralising antibody targets will be shot to pieces, so what’s going to be left of your immune protection?” said Danny Altmann, professor of immunology at Imperial College London.
“And yet, the soundings we’re getting from South Africa seem to be saying that it doesn’t look severe, and the people who are going to hospital are the unvaccinated, rather than the vaccinated, as if vaccination was still buying [them] some cover.”
Then there are T cells – immune cells that recognise and attack virus-infected cells, and educate antibody-producing B cells about the viral risk they are facing.
“We all think that the T cells can see the differences [between variants], and that the T cell repertoire is much more impervious to it, so that might also buy you some protection,” Altmann said.
The question is, how much protection? We know that people who have been double-jabbed can, and do, get infected with the Delta variant – although the chances of this happening are approximately three times lower than if they hadn’t been vaccinated. More importantly, vaccinated individuals are roughly nine times less likely to die if they do become infected.
Although it looks as though infection with Omicron is even more likely, Prof Paul Morgan, an immunologist at Cardiff University, said: “I think a blunting rather than a complete loss [of immunity] is the most likely outcome.
“The virus can’t possibly lose every single epitope on its surface, because if it did that spike protein couldn’t work any more. So, while some of the antibodies and T cell clones made against earlier versions of the virus, or against the vaccines may not be effective, there will be others, which will remain effective.”
Further boosting that protection, by broadening access to third doses of Covid-19 vaccines, is therefore a good idea. Morgan said: “If half, or two-thirds, or whatever it is, of the immune response is not going to be effective, and you’re left with the residual half, then the more boosted that is the better.”
For individuals who have been double-jabbed and infected with Delta, the picture is better still. “If you’ve been double-jabbed and then infected with Delta and recovered, then you have got a very broad, very effective immune response, that probably covers pretty much any variant that you can think of,” said David Matthews, professor of virology at the University of Bristol.
This is because such individuals have been exposed to the virus (through infection with Delta) and the spike protein from the original Wuhan strain (through vaccination). “It means you’ve got an antibody response that covers both classic and modern strains and a very broad T cell response, not just against the spike protein, but against all the other proteins that Sars-CoV-2 makes – and that’s incredibly helpful,” Matthews said.
The biggest worry is for those who remain unvaccinated. “If they are right that this virus is even better at transmitting than Delta, and it looks like they are, what will happen is that it will speed up the rate at which this virus finds the unvaccinated and puts them in hospitals, and that will therefore increase the pressure on the NHS,” said Matthews. “That is what will trigger a lockdown, if hospitalisation rates go above a certain threshold, whatever that is.”
There are some reasons to be optimistic, however. The first is that we do n’t yet know how the Omicron variant will behave in a highly vaccinated population, such as the UK’s. “It is quite possible that people who have had two or, better still, three doses of existing vaccines will be well protected against it,” said Dr Peter English, a retired consultant in communicable disease control. “But it is also possible that we will have much less protection from existing vaccines against this new variant. We do not yet have enough information to know.”
Another is the existence of antiviral drugs, such as molnupiravir, to which Omicron should still be responsive. Nearly half a million doses of this twice-daily pill were due to be delivered this month, and will be given as a priority to elderly Covid patients and those with particular vulnerabilities, such as weakened immune systems, through a national study being run by the NHS. Because the drug is most effective when given in the early stages of infection, the MHRA recommends it is used as soon as possible after a positive test for Covid and within five days of symptoms appearing.
Existing therapies, such as the anti-inflammatory drug dexamethasone, are also likely to work against Omicron, because it targets the body’s response to the virus, rather than the virus itself.
Finally, there is the possibility of modifying the existing vaccines to match the Omicron variant, if it really does evade vaccine-induced immune responses to a significant degree – something we won’t know for a number of weeks.
English said: “The mRNA and vector platforms allow very rapid changes to be made to the precise antigens used. This means that it would be possible, relatively quickly (within a matter of months), to produce a vaccine with antigens tailored to a new variant.”
Omicron is undoubtedly a bump in the road leading us out of this pandemic, and quite possibly a major pothole, but based on what we know so far, it seems unlikely to send us back to where we were a year ago. However, the more people who are fully jabbed, and have access to those third doses, the more certain of this we are likely to be.